Weight loss following testosterone treatment in hypogonadal men

Obesity is a global public health problem reaching epidemic levels and has a huge impact on overall health, reduced quality of life and premature death. Testosterone (T) plays an important role in modulating adipogenesis and metabolism of carbohydrates and fats, and reduced plasma T levels have been associated with obesity and type 2 diabetes. However, treatment of obese subjects with T has resulted in marked decreases in fat mass, increases in lean body mass and improved sensitivity to insulin. Furthermore, T treatment in hypogonadal men has resulted in improvements in various cardiovascular parameters including serum LDL-cholesterol, blood pressure and heart rate.

The effect of T treatment on anthropometric parameters was investigated in 255 men being treated with testosterone replacement therapy (TRT). This study was not designed to treat obesity or induce weight loss but rather examined measures of obesity recorded in hypogonadal men receiving T treatment for various medical conditions. The men were between 33 and 69 years of age, however, they were predominantly elderly (mean age, 58 years). Data were collected from patients treated in a single urologist’s office and all received treatment with parenteral testosterone undecanoate (TU) 1,000 mg. The study reported changes in body weight, body mass index (BMI) and waist circumference following long-term T treatment for up to 5 years. This study has the longest duration to date of any study using testosterone in hypogonadal men.

Key Points

Low T has been associated with the development of obesity and other related conditions such as type 2 diabetes1,2

Lifestyle changes (diet and exercise) are typically recommended by physicians to combat obesity but weight loss is often modest and not sustainable over long periods of time3-5

The effect of T replacement therapy on weight and waist circumference was assessed in hypogonadal men receiving treatment for various medical conditions over a period of up to 5 years. The study reported substantial reductions in body weight, BMI and waist circumference following long-term treatment with T, and these reductions continued year after year over the 5-year observation period. Significant and marked weight loss occurred in almost all patients (95%). No significant weight gain was observed in obese or overweight men

A reduction in waist circumference was observed in 97% of patients, declining from 107.2 ± 9.1 cm to 98.5 ± 7.4 cm

The reductions in body weight and waist circumference were statistically significant at the end of each year compared with the previous year, over the 5-year study duration (p<0.0001)

A consistent and progressive decrease in BMI was also observed year after year during the 5-year observation period. At baseline BMI was 33.9 ± 5.5 and decreased to 32.4 ± 4.9 after 1 year, 31.3 ± 4.6 after 2 years, 30.6 ± 4.1 after 3 years, 30.2 ± 3.8 after 4 years and 29.1 ± 3.1 kg/m2 after 5 years

The decline in BMI was most marked in obese men, followed by overweight men but with minimal changes observed in men whose BMI was within the normal range at baseline

Moderate weight gain was observed only in men with normal weight at baseline, all of whom had co-morbidities including Crohn’s disease, ulcerative colitis, leukemia and Hodgkin’s lymphoma

The potential benefit and contribution of T treatment in combating obesity in hypogonadal men is new and unexpected, as such profound effects of T treatment on weight had not previously been reported. Previous T studies have been short-term and thus showed no or only modest effects on weight

One of the longest studies, a 3-year placebo-controlled pilot study in men treated with TU, reported a decrease in waist circumference (a reliable indicator of visceral obesity) of 13 cm10

Combined with lifestyle changes, T may be a useful tool for facilitating weight loss in hypogonadal men

What is known

Obesity is a global health concern, growing to epidemic levels and leading to extensive health problems and morbidity.11 T plays a crucial role in energy utilization via a number of metabolic pathways1,12 and it upregulates various enzymes and transcriptional factors involved in metabolic function, particularly in mitochondria.13
T is known to inhibit lipoprotein lipase activity and triglyceride uptake resulting in rapid turnover of triglycerides and mobilization of lipids. Treatment with T has consistently shown a decrease in fat mass and increase in lean body mass.6-9 In addition, as T treatment is known to improve mood and alleviate fatigue, the patient is more motivated to pursue an active lifestyle, thus further increasing energy expenditure and contributing to weight loss. Interest in T treatment has grown recently following findings in pre-clinical and clinical studies that have implicated a role for T in the development of obesity.

What this study adds

This is the first study to report that T may have profound effects in facilitating weight loss in hypogonadal men. The magnitude of the weight loss observed in this study was unexpected as it was not designed to treat obesity or induce weight loss but rather examined measures of obesity recorded in hypogonadal men receiving T treatment for various medical conditions.

Earlier studies have been conducted over a relatively short time period, partly because the duration of placebo-controlled designed trials is limited by the risks of withholding treatment in patients with hypogonadism for long time periods. This present study was an observational study that assessed the association of T treatment and weight loss and included ‘real world’ data collected over the longest time period to date (5 years). Although the study was based on observational data, these data are considered robust as weight loss had not been expected and therefore men were not influenced by any suggestion that they may lose weight. Furthermore, the patients were not selected for any criteria other than hypogonadism; they presented with various comorbidities or were referred by other specialists with a suspicion of hypogonadism (e.g. osteoporosis).

This study reported substantial reductions in body weight, BMI and waist circumference following long-term treatment with T and these reductions were consistent and progressive over the 5-year observation period. Significant and marked weight loss occurred in almost all patients (95%) with the largest reductions in obese men at baseline.

Therefore, T therapy may be a useful tool to aid management of obesity in hypogonadal men. Nonetheless, long-term safety studies in hypogonadal men are required to provide further evidence that T is a safe and effective treatment to facilitate weight loss in this patient group.

Figure 1: Reduction in body weight (kg) in hypogonadal men in response to testosterone treatment over the course of 60 months